title: Circulating leukocyte and carotid atherosclerotic plaque telomere length: interrelation, association with plaque characteristics, and restenosis after endarterectomy.
abstract: OBJECTIVE
  Shorter leukocyte telomeres are associated with atherosclerosis and predict future heart disease. The goal of the present study was to determine whether leukocyte telomere length is related to atherosclerotic plaque telomere length and whether it is associated with plaque characteristics or recurrence of disease.
  
  
  RESULTS
  Telomere length was measured by real-time quantitative polymerase chain reaction in atherosclerotic plaques and leukocytes in patients with carotid atherosclerosis undergoing carotid endarterectomy (n=684) and of leukocytes in age- and gender-balanced subjects without clinical atherosclerosis (n=780). Leukocyte telomere length was shorter in patients versus controls (0.99 [interquartile range (IQR): 0.79 to 1.26] versus 1.06 [0.80 to 1.39]; P=0.0007). Plaque telomeres were longer than leukocyte telomeres (1.42 [IQR: 1.21 to 1.77] versus 1.01 [IQR: 0.75 to 1.34]; P<1.00×10(-6)) and independent of age. Leukocyte and plaque telomere length were only weakly correlated (correlation coefficient r2=0.04, P=0.03). Patients, whose plaques showed marked macrophage infiltration and large lipid core, had longer plaque telomeres (1.61 [IQR: 1.32 to 2.04] versus 1.40 [IQR: 1.15 to 1.57]; P=0.006) and shorter leukocyte telomeres (0.88 [IQR: 0.75 to 1.20] versus 1.03 [IQR: 0.83 to 1.34]; P=0.02). Plaque telomere length was associated with restenosis 1 year after endarterectomy (OR 1.58±0.206; P=0.026 per SD decrease of plaque telomere length).
  
  
  CONCLUSIONS
  Leukocyte telomere length is associated with the presence of atherosclerotic carotid plaques but is not a proxy for local plaque telomere length. Plaque telomere length is related to plaque characteristics and development of restenosis following endarterectomy.
authors.affiliation: University Medical Centre Groningen, Department of Cardiology, University of Groningen, Hanzeplein 1, PO Box 9700 RB Groningen, the Netherlands.
authors.forename: Jardi
authors.initials: J
authors.lastname: Huzen
authors.forename: Wouter
authors.initials: W
authors.lastname: Peeters
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Liza S M
authors.initials: LS
authors.lastname: Wong
authors.forename: Veryan
authors.initials: V
authors.lastname: Codd
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Bart J G L
authors.initials: BJ
authors.lastname: de Smet
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
mesh_terms: D000368:Aged; D016893:Carotid Stenosis / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D016894:Endarterectomy, Carotid / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes / Q000276:immunology*; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D009426:Netherlands; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D016615:Telomere / Q000648:ultrastructure*; D013997:Time Factors; D016896:Treatment Outcome